Analysis of SCF⁺ cardiac cells in mice

Abstract

Proper regulation of c-kit receptor tyrosine kinase by its ligand, Stem Cell Factor (SCF), is essential for survival, growth, migration and differentiation of many types of stem/progenitor cells. However, its role in the heart has remained elusive. The nature of c-kit<strong>⁺</strong> cardiac cell populations has been at least partially clarified by the use of recently developed genetic mouse models, whereas the cell populations expressing the endogenous ligand SCF have not been identified. <br /> In my current study, I have therefore analyzed the expression pattern of SCF during mouse heart development and after cardiac injury by taking advantage of a transgenic mouse line, SCF-CreER<strong>^T2</strong>, which expresses a Cre/mutated human estrogen receptor (ER<strong>^T2</strong>) fusion protein and a tdTomato fluorescence protein under control of the SCF promoter. This model enables to identify SCF expressing cells in the heart and to genetically trace the lineage of these cells under various conditions. I discovered that SCF was expressed in two previously undefined cell populations including small-arterial like vascular endothelial cells and embryonic like newly differentiated cardiomyocytes. I also examined the expression pattern of SCF after myocardial infarction in adult mice and found substantial decrease of SCF<strong>⁺</strong> cells in the border and infarct area of the injured heart. <br /> In conclusion, this study did not support the notion that potential C-kit<strong>⁺</strong> stem cells contribute to the regeneration of infarcted hearts. Instead, I found that SCF expression marked small-arterial like coronary vascular endothelial cells and newly differentiated cardiomyocytes. Further molecular characterization of these two cell populations could provide useful insights into the regulatory mechanisms of coronary arteriogenesis and cardiomyocyte proliferation.